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PLoS One ; 10(11): e0141618, 2015.
Article in English | MEDLINE | ID: mdl-26545108

ABSTRACT

Cancer has become a major problem worldwide due to its increasing incidence and mortality rates. Both the 37kDa/67kDa laminin receptor (LRP/LR) and telomerase are overexpressed in cancer cells. LRP/LR enhances the invasiveness of cancer cells thereby promoting metastasis, supporting angiogenesis and hampering apoptosis. An essential component of telomerase, hTERT is overexpressed in 85-90% of most cancers. hTERT expression and increased telomerase activity are associated with tumor progression. As LRP/LR and hTERT both play a role in cancer progression, we investigated a possible correlation between LRP/LR and telomerase. LRP/LR and hTERT co-localized in the perinuclear compartment of tumorigenic breast cancer (MDA_MB231) cells and non-tumorigenic human embryonic kidney (HEK293) cells. FLAG® Co-immunoprecipitation assays confirmed an interaction between LRP/LR and hTERT. In addition, flow cytometry revealed that both cell lines displayed high cell surface and intracellular LRP/LR and hTERT levels. Knock-down of LRP/LR by RNAi technology significantly reduced telomerase activity. These results suggest for the first time a novel function of LRP/LR in contributing to telomerase activity. siRNAs targeting LRP/LR may act as a potential alternative therapeutic tool for cancer treatment by (i) blocking metastasis (ii) promoting angiogenesis (iii) inducing apoptosis and (iv) impeding telomerase activity.


Subject(s)
Gene Knockdown Techniques , Receptors, Laminin/deficiency , Receptors, Laminin/genetics , Ribosomal Proteins/deficiency , Ribosomal Proteins/genetics , Telomerase/metabolism , Cell Nucleus/metabolism , Gene Expression Regulation/genetics , HEK293 Cells , Humans , Protein Transport/genetics , RNA, Small Interfering/genetics , Receptors, Laminin/metabolism , Ribosomal Proteins/metabolism
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